We propose studies with the objective: to develop improved methods of diagnosing malignant melanoma, in terms of lesion detectability and site, extent of local invasion, and evidence for distant metastasis. We will utilize a monoclonal antibody which binds with high affinity to the oncofetal antigen, "p97", which has been recently discovered by the Hellstrom's group, and is abundantly expressed on a high proportion of human malignant melanomas, but not on normal adult tissues. For clinical imaging of human tumors, we will utilize single photon emission tomography (SET), based on a GE-400 T gamma camera system and computerized tomography developed by our collaborators at Seattle Veterans Medical Center, Drs. D.L. Williams and J.L. Ritchie. Our experimental approach includes production of homogeneous, monoclonal, anti-p97 antibody of various subclasses using the hybridoma technique of Kohler and Milstein. The antibodies will be radiolabelled with 131I, 123I, or 111In and their affinity characterized by in vitro methods which have been developed by one of us (J.P. Brown). Human melanoma tissue will be obtained by biopsy and the amount of p97 assayed by an immunoassay using radioiodinated FAbs (R.G. Woodbury and J.P. Brown), xenografts from these tumors will be grown in athymic mice (by Dr. P.W. Wright) and biodistribution studies will be performed using anti-p97 antibody. Tumor concentrations of radiolabelled antibody will be correlated with the amount of p97 assayed in the tumor tissues and comparison will be made to radiolabelled mouse antibody (nonspecific) to assess specificity of binding of anti-p97 antibody. Relative tumor concentrations of various proteolytic fragments (Fab, F(ab')2) and subclasses of anti-p97 IgG will be tested. Clinical imaging studies will be performed using the optimal antibody preparations in highly selected patients who have high levels of p97 documented on their tumors, using SET. Whenever possible, tissue samples will be obtained to correlated scan appearance with measured tumor concentration of radiolabelled monoclonal antibody.